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Background: 4-part proximal humerus fractures are complex injuries that are often associated with comminution of the greater tuberosity. The purpose of this study is to evaluate the functional outcomes of 4-part humerus fractures that are treated with reverse total shoulder arthroplasty (rTSA) and correlate these outcomes with the healing status of the greater tuberosity. Material and methods: A retrospective observational study was performed including 65 patients who underwent rTSA following a 4-part proximal humerus fracture. These patients were categorized into 3 groups according to the healing status of the greater tuberosity: patients with healed greater tuberosity in an anatomical position (group A, n = 43), patients with non-union of the greater tuberosity but in anatomical position (group B, n = 14), and patients with resorption or non-union of the greater tuberosity not in anatomical position (group C, n = 8). The Constant-Murley score and range of motion were recorded for each patient at 12 months postoperatively. The clinical and radiographical outcomes of the 3 groups were compared. Results: Patients with healed greater tuberosity (group A) had higher range of motion compared to patients with greater tuberosity migration or reabsorption (group C) regarding forward flexion (130° vs 80°, p < 0.001), abduction (110° vs 65°, p < 0.001) and external rotation (20° vs 10°, p = 0.004). However, no significant changes regarding forward flexion (130° vs 125°, p = 0.67), abduction (110° vs 100°, p = 0.60) and external rotation (20° vs 25°, p = 0.37) were noted between patients with healed greater tuberosity (group A) and those with non-united greater tuberosity that remained attached to the humeral prosthesis (group B). Similarly, Constant- Murley score was similar between patients of group A and group B (65.0 vs 61.5, p = 0.53), while it was higher in patients of group A compared to those of group C (65.0 vs 39.0, p = 0.053). Conclusions: The outcomes of this study indicate that reliable recovery regarding range of motion and functional status can be achieved in patients who undergo rTSA due to 4-part proximal humerus fractures, as long as the greater tuberosity remains in close proximity to the humeral prosthesis, even if it has signs of non-union with no continuity to the adjacent humerus. [ABSTRACT FROM AUTHOR]

Objectives: Treatment of 5th metatarsal fractures via direct discharge from virtual fracture clinic (VFC) has become common practice in the NHS. We aim to assess the functional outcome and incidence of non-union in a series of 5th metatarsal base fractures, exposed to 1-year of follow-up. Methods: 194 patients who sustained a fracture between the period February 2019 to April 2020 were included, referred via the VFC pathway. Radiographs were reviewed to classify in which zone, the fracture occurred along with union on subsequent follow-up. Telephone follow-up was used to measure patient functional outcomes (EQ-5D & FAAM survey) and satisfaction with the VFC service. Results: Off 194 patients, 53 (27.3%) had zone 1, 99 (51%) had zone 2, and 42 (21.6%) had zone 3 fractures. 80 were discharged directly from VFC, with 114 patients being offered at least one face to face clinic follow-up. Six (3.1%) patients had clinical and radiological evidence of non-union; 4 in zone 2, and 2 in zone 3. No zone 1 injuries were identified as a non-union. Only 2 patients had surgery, 1 of which was for symptomatic non-union. Of the 6 non-union patients, 1 had surgery, 4 did not wish to have surgery and the final non-union patient was deemed unsuitable for surgery. Conclusion: The VFC is an effective way of managing 5th metatarsal fractures, with high patient satisfaction. Conservative management has excellent outcomes, with a low percentage of zone 2 and 3 injuries developing a symptomatic non-union. Functional outcome surveys provide further reassurance. [ABSTRACT FROM AUTHOR]

Background: Fracture healing is a very complex and well-orchestrated regenerative process involving many cell types and molecular pathways. Despite the high efficiency of this process, unsatisfying healing outcomes, such as non-union, occur for approximately 5–10% of long bone fractures. Although there is an obvious need to identify markers to monitor the healing process and to predict a potential failure in callus formation to heal the fracture, circulating bone turnover markers' (BTMs) utility as biomarkers in association with radiographic and clinical examination still lacks evidence so far. Methods: A systematic review on the association between BTMs changes and fracture healing in long bone non-union was performed following PRISMA guidelines. The research papers were identified via the PubMed, Cochrane, Cinahl, Web of Science, Scopus, and Embase databases. Studies in which the failure of fracture healing was associated with osteoporosis or genetic disorders were not included. Results: A total of 172 studies were collected and, given the inclusion criteria, 14 manuscripts were included in this review. Changes in circulating BTMs levels were detected during the healing process and across groups (healed vs. non-union patients and healthy vs. patients with non-union). However, we found high heterogeneity in patients' characteristics (fracture site, gender, and age) and in sample scheduling, which made it impossible to perform a meta-analysis. Conclusions: Clinical findings and radiographic features remain the two important components of non-union diagnosis so far. We suggest improving blood sample standardization and clinical data collection in future research to lay the foundations for the effective use of BTMs as tools for diagnosing non-union. [ABSTRACT FROM AUTHOR]

Abstract Background Few contemporary US-based long bone non-union analyses have recently been published. Our study was designed to provide a current understanding of non-union risks and costs, from the payers' perspective. Methods The Merative™ MarketScan® Commercial Claims and Encounters database was used. Patients with surgically treated long bone (femur, tibia, or humerus) fractures in the inpatient setting, from Q4 2015 to most recent, were identified. Exclusion criteria included polytrauma and amputation at index. The primary outcome was a diagnosis of non-union in the 12 and 24 months post-index. Additional outcomes included concurrent infection, reoperation, and total healthcare costs. Age, gender, comorbidities, fracture characteristics, and severity were identified for all patients. Descriptive analyses were performed. Crude and adjusted rates of non-union (using Poisson regressions with log link) were calculated. Marginal incremental cost of care associated with non-union and infected non-union and reoperation were estimated using a generalized linear model with log link and gamma distribution. Results A total of 12,770, 13,504, and 4,805 patients with femoral, tibial, or humeral surgically treated fractures were identified, 74–89% were displaced, and 18–27% were comminuted. Two-year rates of non-union reached 8.5% (8.0%–9.1%), 9.1% (8.6%–9.7%), and 7.2% (6.4%–8.1%) in the femoral, tibial, and humeral fracture cohorts, respectively. Shaft fractures were at increased risk of non-union versus fractures in other sites (risk ratio (RR) in shaft fractures of the femur: 2.36 (1.81–3.04); tibia: 1.95 (1.47–2.57); humerus: 2.02 (1.42–2.87)). Fractures with severe soft tissue trauma (open vs. closed, Gustilo III vs. Gustilo I–II) were also at increased risk for non-union (RR for Gustilo III fracture (vs. closed) for femur: R = 1.96 (1.45–2.58), for tibia: 3.33 (2.85–3.87), RR for open (vs. closed) for humerus: 1.74 (1.30–2.32)). For all fractures, younger patients had a reduced risk of non-union compared to older patients. For tibial fractures, increasing comorbidity (Elixhauser Index 5 or greater) was associated with an increased risk of non-union. The two-year marginal cost of non-union ranged from $33K-$45K. Non-union reoperation added $16K–$34K in incremental costs. Concurrent infection further increased costs by $46K–$86K. Conclusions Non-union affects 7–10% of surgically treated long bone fracture cases. Shaft and complex fractures were at increased risk for non-union.

Background: Few contemporary US-based long bone non-union analyses have recently been published. Our study was designed to provide a current understanding of non-union risks and costs, from the payers' perspective. Methods: The Merative™ MarketScan® Commercial Claims and Encounters database was used. Patients with surgically treated long bone (femur, tibia, or humerus) fractures in the inpatient setting, from Q4 2015 to most recent, were identified. Exclusion criteria included polytrauma and amputation at index. The primary outcome was a diagnosis of non-union in the 12 and 24 months post-index. Additional outcomes included concurrent infection, reoperation, and total healthcare costs. Age, gender, comorbidities, fracture characteristics, and severity were identified for all patients. Descriptive analyses were performed. Crude and adjusted rates of non-union (using Poisson regressions with log link) were calculated. Marginal incremental cost of care associated with non-union and infected non-union and reoperation were estimated using a generalized linear model with log link and gamma distribution. Results: A total of 12,770, 13,504, and 4,805 patients with femoral, tibial, or humeral surgically treated fractures were identified, 74–89% were displaced, and 18–27% were comminuted. Two-year rates of non-union reached 8.5% (8.0%–9.1%), 9.1% (8.6%–9.7%), and 7.2% (6.4%–8.1%) in the femoral, tibial, and humeral fracture cohorts, respectively. Shaft fractures were at increased risk of non-union versus fractures in other sites (risk ratio (RR) in shaft fractures of the femur: 2.36 (1.81–3.04); tibia: 1.95 (1.47–2.57); humerus: 2.02 (1.42–2.87)). Fractures with severe soft tissue trauma (open vs. closed, Gustilo III vs. Gustilo I–II) were also at increased risk for non-union (RR for Gustilo III fracture (vs. closed) for femur: R = 1.96 (1.45–2.58), for tibia: 3.33 (2.85–3.87), RR for open (vs. closed) for humerus: 1.74 (1.30–2.32)). For all fractures, younger patients had a reduced risk of non-union compared to older patients. For tibial fractures, increasing comorbidity (Elixhauser Index 5 or greater) was associated with an increased risk of non-union. The two-year marginal cost of non-union ranged from $33K-$45K. Non-union reoperation added $16K–$34K in incremental costs. Concurrent infection further increased costs by $46K–$86K. Conclusions: Non-union affects 7–10% of surgically treated long bone fracture cases. Shaft and complex fractures were at increased risk for non-union. [ABSTRACT FROM AUTHOR]

To compare the efficacy of recombinant human bone morphogenetic proteins (rhBMPs) and autologous bone graft (ABG) on the healing of long bone non-union. A systematic literature search was conducted on PubMed, Web of Science, Cochrane Library, and CNKI up to December 2021. Two authors independently screened the studies, extracted data, and assessed the quality of the trials. A Meta-analysis was performed using state software (version 12.0). A total of 14 studies were included in this meta-analysis. Overall, there was no significant difference between the rhBMPs group and the ABG group in terms of healing rate (RR = 1.04, 95% CI = 0.96–1.12, p = 0.365) and healing time (SMD = −0.31, 95% CI = −0.76–0.14, p = 0.175). Subgroup analysis showed rhBMPs lead to higher healing rates (RR = 1.35, 95% CI = 1.17–1.56, p < 0.001), and shorter healing time (SMD = −0.65, 95% CI = −1.08 to −0.22, p = 0.003) in the subgroup of moderate-quality studies. Sensitivity analysis proved that our conclusions were relatively robust. No significant publication bias was recognized in all studies (Begg's test, p = 0.193; Egger's test, p = 0.307). RhBMPs or combined with allografts bone, inorganic bone was a valid alternative to ABG for the treatment of long bone non-union. • The largest scale meta-analysis for rhBMPs in long bone non-union. • RhBMPs can replace autologous bone graft (ABG) in these cases; • The combination of rhBMPs and ABG was not desirable in these cases; • The outcomes were associated with the quality of the included studies. [ABSTRACT FROM AUTHOR]

Following a ground-level fall on an extended arm, proximal humerus fractures are typical fractures often found in elderly individuals with osteoporotic bone.1,2 Managing fractures in the proximal part of humerus might be difficult if the fracture associated with it is complex.3 While many patients benefit from surgery, others, particularly older individuals with valgus affected proximal humerus fractures, are effectively handled non-surgically. Age-related complicated fractures in the proximal part of humerus which might be 3 part or 4 parts are increasingly being treated with reverse shoulder arthroplasty.4,5,6 76 yr Old aged postmenopausal women allegedly fall down from her bike and was brought to our hospital. A fractured proximal humerus was discovered on radiology.8 The indications for the usage of new technique reverse shoulder arthroplasty have been in the increasing trends over few decades which include deficiency at the rotator cuff muscle, major nonrecoverable tears at the rotator cuff muscles, fractures less than 3 weeks, native treatment which may lead to recurrent dislocations, non-union and most common complication malunion and for revision arthroplasty, and for any lifesaving salvage conditions.7,8,9 The patient had reverse shoulder arthroplasty, and all of his or her functions were fully recovered. The majority of patients report pain reduction and better function, and patient satisfaction with RTSA may be high.10,11,12 The longterm effects remain unclear, despite the fact that the implant survival rate seems to be satisfactory in the short term. Contrary to expectations, Reverse Shoulder Arthroplasty is linked to a greater rate and wider range of problems. To make this therapy as effective as possible for numerous shoulder disorders, improvements in prosthesis design, surgeon expertise, and clinical outcomes are required. [ABSTRACT FROM AUTHOR]

Introduction: Non-union occurs when a fracture fails to adequately heal, and requires additional intervention to achieve union. The purpose of this scoping review is to provide a high-level overview of the existing non-union management literature. This review aims to highlight the current literature on non-union management, as well as identify key areas that require future research to provide a better understanding of potential non-union management strategies.Methods: This study utilized the scoping review framework from Arksey and O'Malley All relevant literature on non-union management was systematically searched for within the OVID Medline, OVID Embase, and Web of Science databases. As a scoping review, this study aimed to identify the high-level trends in non-union literature. This was assessed through a visual and numerical summary of the general themes in non-union literature, as well as the timeline in which these trends have occurred.Results: The literature search identified 8081 articles, of which 2210 articles were included. There is a large body of evidence for various surgical treatment options for non-union. The literature suggests healing rates between 80 and 100 percent for commonly utilized surgical procedures, such as plating with bone graft for long bones. Despite these beneficial healing rates, the requirement of a surgery creates a large socioeconomic burden. The possibility for bone growth stimulator (BGS) options to achieve non-union healing rates in a similar realm as surgical options suggests that the use of a BGS may be a beneficial option prior to surgical intervention, as this would potentially reduce the number of patients who would otherwise require surgery.Conclusion: A large body of evidence exists on non-union management, which is largely comprised of case series and reports. The most commonly assessed non-unions include the tibia, wrist, and femur. Bone grafting, plating, and nailing are the most investigated treatment options. BGS are a non-operative treatment options for non-union that provide similar healing rates to surgical options in certain indications within initial observational data. BGS are a potential option for non-operative management of non-unions to reduce socioeconomic burdens of surgical intervention, with a need for further high-quality investigation in this therapeutic area. [ABSTRACT FROM AUTHOR]

Healing problems of segmental fractures of long bones are some of the most common complications. The purpose of this study is to review the incidence and pathogenesis of healing problems of segmental fractures of long bones. This is a simple literature review using the Pubmed database. Papers were searched with the use of the following keywords: ("segmental fractures") AND ("femur" OR "femoral" OR "tibia" OR "tibial" OR "humerus" OR "humeral" OR "forearm" OR "radius" OR "ulna). Moreover, the reference lists of the included papers were scanned for additional studies. Prospective or retrospective evaluating union rate and healing problems after the management of segmental fractures in long bones (femur, tibia, humerus, forearm) were included in this review. The search retrieved a total of 118 papers. After application of exclusion criteria, 30 studies were left in the present review. Successful healing of segmental fractures of long bones depends on the initial condition of the fracture, and surrounding soft tissues, since these high energy injuries may compromise the bone fragments blood supply. The rate of non-union is higher in open and severely comminuted fractures. Intramedullary nailing of segmental fractures of long bones seems to be the surgical option with the least healing problems. [ABSTRACT FROM AUTHOR]

Introduction: Low-intensity pulsed ultrasound (LIPUS) is a non-invasive treatment modality for delayed union or non-union of acute fractures. We aimed to assess the current use of LIPUS at a national level in the United Kingdom, why and how clinicians use it, what treatment protocols are followed, and what the current perceptions are on this technology.Methodology: Using a detailed online survey compromised of 20 questions delivered to known LIPUS users, we were able to collect qualitative data on indication of use, type of machine used, personal views on the technology, frequency of usage, and treatment protocols. Each question was peer-reviewed to exclude bias.Results: A total of 70 respondents completed the survey. LIPUS was used by most clinicians for cases of non-union (N = 55, 78.5%) and delayed union (N = 51, 72.8%). The majority of respondents personally used a LIPUS device between 1 and 5 times in 12 months (N = 38, 54.3%). Most considered LIPUS a failure after three to six months of treatment without clinical improvement (N = 39, 55.7%). A total of 32 respondents (45.7%) mentioned the need for funding approval before accessing LIPUS technology. Poor revision surgery candidates (N = 48, 68.6%) and atrophic non-union (N = 46, 65.7%) were the most frequently cited reasons for using LIPUS technology as treatment. Most participants (N = 48, 68.6%) considered LIPUS to be cost-effective. Despite most clinicians being comfortable with the use of LIPUS, some respondents did not understand the basic science underpinning the technology nor could explain the need for LIPUS to patients comfortably.Conclusion: LIPUS technology may have a significant role to play in the treatment of orthopaedic fracture related pathology. Regular users perceived the technology to be cost-effective and efficacious. Further research should standardize treatment protocols and aim to establish a national LIPUS registry. [ABSTRACT FROM AUTHOR]

Background: Non-unions and chronic instability of the pelvis remain rare complications after complex high velocity injuries with vertical and rotational instability of the pelvis. Treatment options are insufficiently supported by data evidence due to the rareness of this condition.Patients and Methods: we conducted a single center, retrospective study of all non-unions and pelvic instabilities between 1.1.2008 and 1.1.2019, excluding fragility fractures. Patients' characteristics, fracture patterns, procedures and outcomes with regard to developing treatment options and successful union in the follow-up were obtained.Results: 26 patients were included in this retrospective analysis. The mean age was 55 years (range 34-78 years). Seventy-seven percent of the patients were male. The standard procedure consisted of radical debridement of the non-union, interposition of autologous bone graft and rigid stabilization systems. Three patients were lost to follow up. In the remaining n = 23 patients (88%) consolidation of the non-union was achieved. The mean follow up was 31.3 months (range 6-144). Follow up showed that an iliolumbar fixation seems to be favorable regarding outcome and complications.Discussion: Non-union and remaining instability of the pelvic ring represent a rare complication after high grade pelvic trauma. There are only limited data regarding the incidence and the treatment regimen is based on small study populations only. Based on our findings we recommend to combine autologous bone grafts with rigid fixation systems especially for non-union of the pelvis to restore the posterior sacroiliac arch. [ABSTRACT FROM AUTHOR]

Fracture non-union, prosthetic joint infection and fracture-related infections are complications frequently encountered by the trauma and orthopaedic surgeon. Moreover, they pose a significant socioeconomic and healthcare burden to the society. A clear understanding of the molecular biology surrounding fracture healing, as well as the pathophysiology of orthopaedic-related infections, is of paramount importance to their successful management. The first section of this article aims to explain the basic science critical to the understanding of DNA, RNA, gene and protein expression, and the molecular techniques most commonly deployed in the diagnostic and research fields of trauma and orthopaedics. The second section provides a general overview of the molecular physiology of fracture healing and biofilm, the molecular characteristics and genetic predisposition of fracture non-union, followed by discussing recent advances in molecular techniques used in the diagnosis and treatment of fracture non-union, prosthetic joint infection and fracture-related infections. [ABSTRACT FROM AUTHOR]

Introduction: Within the last few decades, focused high-energy extracorporeal shockwave therapy (ESWT) has proven to be an effective alternative to standard of care revision surgery in delayed healing fractures or manifest non-unions in various anatomical regions. Materials and methods: A retrospective multi-variant analysis of an open prospective, single-armed clinical study was conducted. Patients receiving focused high-energy ESWT for a delayed healing or an apparent non-union of a humeral fracture between January 1999 and December 2015 at a single trauma center were included in the study. Bony healing was defined as cortical continuity in three of four cortices and pain-free force loading and evaluated using CT scans and clinical examination at three- and six-month follow-ups after ESWT. Results: A total of 236 patients were included. N = 93 (43.8%) showed bony consolidation three months after ESWT and n = 105 (52.5%) after six months. Sub-group analysis showed significantly better healing for the proximal metaphyseal humerus (66.7% after six months, n = 42) compared to the diaphyseal region (48.1%, n = 133) and distal metaphyseal humerus (48.1%, n = 25). Regression analysis indicated significantly increased healing rates for patients of younger ages (p = 0.001) and a fracture diastasis of less than 5 mm (p = 0.002). Conclusion: The findings of this study indicate that ESWT can be considered as a treatment option for a well-selected patient population despite the lower healing rates compared to other anatomical regions. [ABSTRACT FROM AUTHOR]

Background: Long bone fractures display significant non-union rates, but the exact biological mechanisms implicated in this devastating complication remain unclear. The combination of osteogenetic and angiogenetic factors at the fracture site is an essential prerequisite for successful bone regeneration. The aim of this study is to investigate the results of the clinical implantation of growth factors for intraoperative enhancement of osteogenesis for the treatment of long bone fractures and non-unions. Methods: A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed and Web of Science databases from the date of inception of each database through to 10 January 2022. Specific inclusion and exclusion criteria were applied in order to identify relevant studies reporting on the treatment of upper and lower limb long bone non-unions treated with osteoinductive or cellular factors. Results: Overall, 18 studies met the inclusion criteria and examined the effectiveness of the application of Bone Morphogenetic Proteins-2 and -7 (BMPs), platelet rich plasma (PRP) and mesenchymal stem cells (MSCs). Despite the existence of limitations in the studies analysed (containing mixed groups of open and close fractures, different types of fractures, variability of treatment protocols, different selection criteria and follow-up periods amongst others), their overall effectiveness was found significantly increased in patients who received them compared with the controls (I2 = 60%, 95% CI = 1.59 [0.99–2.54], Z =1.93, p = 0.05). Conclusion: Administration of BMP-2 and -7, PRP and MSCs were considered effective and safe methods in fracture treatment, increasing bone consolidation, reducing time to repair and being linked to satisfactory postoperative functional scores. [ABSTRACT FROM AUTHOR]

• Regenerative medicine approaches offer new opportunities in reinterventions of patients with atrophic pseudoarthrosis. • Clinical use of mesenchymal stromal cell-based tissue-engineered products (TEP) is feasible and safe. • In our study, TEP and iliac crest autograft showed no difference in terms of efficacy. • Our results support the use of TEP in patients ineligible for iliac crest harvesting. Atrophic pseudoarthrosis is a serious complication with an incidence of 5–10 % of bone fractures located in the diaphysis of long bones. Standard treatments involve aggressive surgical procedures and re-interventions requiring the use of autografts from the iliac crest as a source of bone-forming biological activity (Standard of Care, SoC). In this context, regenerative ex vivo expanded osteogenic cell-based medicines could be of interest. Particularly, Mesenchymal Stromal Cells (MSC) offer new prospects to promote bone tissue repair in pseudoarthrosis by providing biological activity in an osteoconductive and osteoinductive environment. We conducted a phase IIa, prospective, randomised, parallel, two-arms, open-label with blinded assessor pilot clinical trial to compare SoC vs. a tissue-engineered product (TEP), composed of autologous bone marrow (BM)-derived MSCs loaded onto allogeneic decellularised, lyophilised spongy bone cubes, in a cohort of 20 patients with non-hypertrophic pseudoarthrosis of long bones. Patients were followed up for 12 months. Radiological bone healing was evaluated by standard X-ray and computed tomography (CT) scanning. Quality of life was measured using the EUROQOL-5D questionnaire. Ten patients were randomized to TEP and 10 to SoC with iliac crest autograft. Manufacturing of TEP was feasible and reproducibly achieved. TEP implantation in the bone defect was successful in all cases and none of the 36 adverse events (AE) reported were related to the treatment. Efficacy analyses were performed in the Full Analysis Set (FAS) population, which included 17 patients after 3 patients withdrew from the study. The degree of consolidation, estimated by measuring Hounsfield units (HU) on CT, showed no significant differences between the two treatment groups at 12 months post treatment (main efficacy variable) (p = 0.4835) or at 6 months. Although only a small number of patients were included in our study, it is notable that no significant differences were observed between the experimental treatment and SoC, thus suggesting TEP as an alternative where autograft is not available or contraindicated. [ABSTRACT FROM AUTHOR]

The use of osteoanabolic agents to accelerate fracture healing has been of enhanced interest in Orthopaedics.Parathyroid hormone administration has a potent ability to increase osteoblastic activity at fracture union site. Studies have largely accepted it and its beneficial effect on fracture healing with a more rapid development of the reparative callus. They are of great help in functional rehabilitation and healthy fracture healing. We have studied its effect on functional status and fracture healing in thirty patients form semi-urban population aged between 28 to 90 years, from January 2018 to March2021. Different bones, fixed with various methods of fixation as per the need of the case, were included in the study. Apart from preoperative assessment of the quality of the bone and the status of the fracture, certain intraoperative findings were documented for the study. Both preoperative and intra-operative points are considered for the study. The intra-operative findings considered are Medullary canal of larger diameter than usual for the age, Thin cortex at the fractured part, Drill holes made effortless, Screw fixation felt as not optimum, Some screws are backed out, during overall fixation of the fracture, Further fractures occurred intra-operative without significant stress. Other factors were also taken to make a score of 18. Selection of patients was based on having at least 9 out of these 18 points. In all the cases only radiographic assessment was done. Due to logistic reasons, no dexa scans were done. Levels of serum calcium, Parathyroid hormone, and 25(OH)D were monitored. They were followed up for a period of 12 months to 18 months. Patients with hypersensitivity to teriparatide or its excipients, history of allergy to drugs, baseline risk factors for osteosarcoma with a history of primary or secondary skeletal cancer, ionising radiation exposure to the skeleton, hypercalcemia with resultant hypercalciuria and urinary stones, were excluded from the study. Selected patients were given injection teriparatide 20ug/d subcutaneous ranging from 4 to 16 weeks. All the patients had good functional rehabilitation, fractures healed in 10-24 weeks. The patients were studied post-operative for fracture union clinically and radiological, improvement in bone quality in radiographs, functional capabilities and overall satisfaction of the patient. These factors showed success in all the patients, with time variables from 12 to 20 weeks. Teriparatide is a promising treatment option for osteoporotic fractures. Possible novel treatment for nonunion and delayed union that may aid in fracture healing and functional rehabilitation. [ABSTRACT FROM AUTHOR]

Fracture non-union results in serious morbidity for patients and a financial burden on healthcare services. Fracture healing is a complex process that involves many chemical signalling molecules and cells. This complexity means there are many stages at which the healing pathway can theoretically be influenced by biologic adjuvants. Biologic adjuvants can be either osteoconductive, osteoinductive or osteogenic. Many laboratory studies have shown success in manipulating the signalling pathways involved in fracture healing. The majority of biologics serve to increase the presence of certain cytokines to stimulate bone forming cells; some agents involve effecting the delivery of early progenitor cells. There have been clinical trials involving multiple biologics, usually in the treatment of tibial non-unions. The clinical trials have shown very limited evidence to support the use of adjuvants in clinical practice. There is a consistent problem translating encouraging laboratory results into similar clinical results with the majority of agents, therefore there remains a lack of clinical evidence to support their use in everyday trauma practice. [ABSTRACT FROM AUTHOR]

Epidemiological and ecological studies on long bone non-unions (NU) are scarce, based on different populations and methodologies. The aim of this study was to produce a descriptive analysis of the femur, tibia, and humerus non-union epidemiology in Spain. Methods Data were obtained from the Minimum Basic Data (Conjunto Mínimo Básico de Datos, CMBD) Hospital Discharge Database of the Spanish Ministry of Health, according to the ICD9-CM coding for diagnoses and procedures, and from the National Institute of Statistics for population, generating secondary databases with the reported cases that included the code 733.82 in a disaggregated manner, by age (categorized in 5 intervals), gender, Spanish region, and calendar year (1997-2015). Percentage of non-unions related to fractures in the previous year, annual prevalence (expressed per 100,000 person-years) and period prevalence (expressed per 100,000 person-period) were calculated by age, gender, and Spanish regions. The Odds ratio (OR) was estimated with a confidence of 95% using a logistic regression model per anatomical site. Results A mean of 235,446 fractures in all locations were annually reported in Spain from 1997 to 2015. Regarding non-union of long bones (femur, tibia and humerus), a total of 37,053 cases were found, representing a yearly mean of 1,950 cases. The proportion of long bone fractures that evolved into a non-union was 4% (1.4% femur, 1.5% tibia, and 1% humerus). The mean annual prevalence rate of NU in Spain was estimated in 4.5 (3.7-4.9) cases per 100,000 persons-year. The overall NU prevalence in Spain was estimated in 86 cases per 100,000 persons. By the type of bone, the period prevalence (per 100,000 persons-period) of the femur NU was 31, of the tibia 33, and of the humerus 22. Conclusions This description of the epidemiology of long bone non-unions in Spain confirms that the overall non-union rate has been stable from 2000 to 2015, higher in the tibia and in the femur compared to the humerus. NU occurred more frequently in aged females than in males in the femur and the humerus, while the tibia non-unions were more frequent in males and younger age. [ABSTRACT FROM AUTHOR]

Background: Non-union after fracture depicts a devastating complication in trauma surgery and studies assessing patient-reported outcome measures after stable bone consolidation are rare. Therefore, we aimed to evaluate the long-term impact of aseptic long bone non-union on the patients' physical health state and psychological wellbeing. For this purpose, quality of life after successful surgical treatment of long bone non-union was assessed.Methods: Sixty-one patients with aseptic long bone non-union surgically treated in our department between November 2009 and March 2019 with achieved bone consolidation were included. Quality of life was evaluated with the EQ-5D and SF-36 outcome instruments as well as with an ICD-10 based symptom rating (ISR) and compared to normative data.Results: With a minimum follow-up time of one year after the last surgery (mean 4.7 ± 2.7 years) the mean physical health component score of the SF-36 was 38.9 ± 13.7 and the mean mental health component score of the SF-36 was 49.0 ± 5.9, indicating lower quality of life compared to German normative values of 48.4 ± 9.4 (p < .001) and 50.9 ± 8.8 (p = 1.61), respectively. The mean EQ-5D index value reached 0.827 ± 0.18 with an EQ-5D VAS rating of 64.4 ± 21.5 compared to scores of 0.922 (p < .001) and 72.9 ± 1.1 (p < .001) obtained from an age-matched reference population. Mean scores of the ISR did not reveal significant psychological symptom burden in any scale, while an individual analysis showed moderate to severe impairments in 11.5% of the patients in total.Conclusion: Even 4.7 years on average after surgically successful treatment of aseptic long bone non-union, patients still report significant lower quality of life in comparison to normative data. Future clinical studies on non-unions should focus on patient-related outcome measures. Newly emerging treatment strategies and interdisciplinary approaches should be implemented to improve the overall quality of life of non-union patients. [ABSTRACT FROM AUTHOR]

Background: Femoral neck fractures in children are rare injuries, occurring due to high-energy trauma. Due to the unique anatomy and blood supply of the proximal femur in growing children, these fractures are notorious for high rates of complications despite appropriate management. Classification of these fractures is according to the Delbet system, which not only guides management but also gives prognostic clues. Multiple fixation methods have been described and there is no consensus on what constitutes the best treatment. Osteonecrosis, non-union, coxa vara and premature physeal arrest are the most frequent complications. Purpose: To review the current knowledge, discuss controversial aspects, and provide suggestions for future research. Methods: We have reviewed the literature on paediatric proximal femur fractures and have provided an evidence-based guide to the diagnosis and management of these injuries. Common complications have been elaborated and options for their prevention and/or management discussed. Conclusion: There is universal agreement that anatomic reduction and stable internal fixation, supplemented by spica immobilization in younger children, are essential to obtain good outcomes. The role of capsular decompression, choice and configuration of implant, and appropriate timing of surgery are aspects that continue to be debated. Multicenter prospective studies are necessary to standardize treatment of these challenging injuries. [ABSTRACT FROM AUTHOR]

Introduction: In adults, treatment of recalcitrant long bone non-union is extremely challenging, with poorly vascularised and atrophic defects unresponsive to standard non-vascularised bone graft treatment. Recent studies have documented the use of free vascularised periosteal flaps to achieve union in refractory long bone fracture non-union, yet its use is not well established. This systematic review aims to assess the evidence for free vascularised periosteal flaps in recalcitrant long bone non-union.Materials and Methods: The MEDLINE®/PubMed® and Embase databases were searched for the Medical Subject Heading (MeSH) terms periosteal flap/vascularised flap/long bone/non-union/non united fracture in accordance with the PRISMA guidelines. Bibliographies were scrutinised for additional articles.Results: Pooled data from 14 studies met the inclusions criteria, comprising 137 cases of non-union, with 117 relating to long bone non-union. Pooled data indicated an overall 99% (116/117) successful union rate. All studies were of mid- to low-level evidence (Level III, IV and V). Only one study directly compared vascularised periosteal flaps to non-vascularised bone grafts, showing union rates of 100% versus 80% and faster time to union (2 versus 5.5 months).Conclusions: Free vascularised periosteal flaps are promising with pooled data showing a 99% success rate in achieving union in refractory long bone non-union. This compares favourably with standard orthopaedic care consisting of revision fixation and non-vascularised bone graft union rates of approximately 80%. However, study design flaws should be addressed by validated outcome measures plus adequate blinding, and further comparative studies with greater patient numbers are required. [ABSTRACT FROM AUTHOR]

Animal models indicate that osteoporosis may negatively influence the fracture healing process, but clinical studies on this topic are scarce. In this study we investigated the effect of osteoporosis on fracture healing in patients with an upper extremity fracture. This retrospective cohort study included all patients aged 50 years or older, with a fracture of the proximal humerus or the distal radius treated in the period June 2012 to July 2015 and a DEXA scan within a year after fracture. The incidence of delayed-union and non-union were compared between patients with or without osteoporosis (BMD T score ≤ −2.5SD). A secondary analysis was performed with a more pragmatically definition; BMD T score ≤ −2.5SD or a proximal humerus fracture with a T-score between −2.5SD and −1.0SD. Osteoporosis was diagnosed in 133/455 patients (29.2%). A total of 461 fractures (distal radius n = 311 and proximal humerus n = 150) were treated. Radiological delayed- or non-union was described in 11/461 cases (2.4%); all proximal humerus fractures of which 6 cases (1.3%) were clinically manifest. The incidence of delayed- or non-union in fracture treatment did not differ between patients with osteoporosis (5/137 fractures) and the patients without osteoporosis (6/324 fractures) (p = 0.27). In the second analysis a significantly higher incidence was found in patients with osteoporosis (10/214 fractures vs 1/247 fractures p = 0.003) The results of this study suggest that osteoporosis does not significantly influence the progress of fracture healing in distal radius and proximal humerus fractures, although there seems to be a tendency towards a negative effect. [ABSTRACT FROM AUTHOR]

Objective: Delayed union, mal-union, non-union and bone loss after long bone fractures have remained a significant predicament in orthopedic practice. To enhance bone union after surgical fixation drugs such as strontium ranelate have shown a promising role. This study aims to assess the effect of strontium ranelate in closed diaphyseal long bone fractures that were managed with intra-medullary nailing and have undergone delayed/non-union. Material and Methods: A randomized clinical trial was conducted at the Department of Orthopedics and Spine Centre, Ghurki Trust Teaching Hospital, Lahore from December 2016 to January 2018. Patients with non-union of long bone fractures were included after taking informed consent. They were randomized to receive placebo or strontium ranelate after nonunion of closed diaphyseal fractures of long bones that were managed with intra-medullary nailing. Fractures were assessed clinically in form of Pain reduction as well as general feeling of wellbeing and radiologically at day 7, 14, 30, 60 and 90. SPSS Version 23 was used for statistical analysis. Results: Of the 101 patients, 50 were randomly assigned to treatment group and 51 were randomly assigned to placebo group. Clinically enhanced fracture healing efficacy of treatment group was 86% (n=43) and radiologically it was 84% (n=42). Clinically enhanced fracture healing efficacy of placebo group was 60.8% (n=31) and radiologically it was 68.6% (n=35). General feeling of wellbeing significantly improved after treatment with strontium ranelate. Conclusion: Systemic strontium ranelate has an exciting and promising role in management of fractures that have undergone non-union/delayed union in non-osteoporotic long bones and should always be considered in such patients. [ABSTRACT FROM AUTHOR]

Purpose: There are several hints that bacterial colonization might be an often overseen cause of non-union. Modern procedures like PCR have been reported to diagnose bacterial colonization with a high degree of accuracy. While PCR is not ubiquitously available, we hypothesize that biopsies from the non-union site are comparable to PCR results reported in the literature. Methods: Retrospective analysis of microbiological results of biopsies from non-unions (femoral or tibial, history of revision surgery, and/or open fracture) with stable osteosynthesis, no clinical signs of local infection were analysed. CRP and leucocyte count were taken on admission. Multiple tissue samples (soft tissue and bone) were from the non-union (1–4 cm incision). Samples were cultivated for 2 weeks and tested following EUCAST protocols using VITEK® 2. Results: 11 tibia- and 7 femur non-union (44 ± 23.9 years), 11 open fractures (1 I°, 6 II°, 4 III° Gustillo Anderson), 0–5 revisions, and 4.1 (± 1.8) tissue samples were taken 8.5 (± 1.7) months after trauma. Cultures were positive in 8/18 (44,4%) (3/18 Propionibacterium acnes, 1/18 S. capitis, and 4/18 S. epidermidis). There was neither a correlation between number of biopsies taken and positive culture results (Pearson R: − 0.0503, R2 0.0025), nor between positive culture results and leucocytes counts (Pearson R: − 0.0245, R2 0.0006) or CRP concentration (Pearson R: 0.2823, R2 0.0797). Conclusion: The results confirm that the presence of bacteria in cases with no clinical signs of infection is a relevant issue. The prevalence of bacteria reported here is comparable that reported from cohorts tested with PCR or sonication. In most cases, there was only one positive biopsy, raising the question whether a contamination has been detected. Thus, to better understand the problem, it is necessary to gather more knowledge regarding the sensitivities and specificities of the different diagnostic procedures. [ABSTRACT FROM AUTHOR]

No evidence exists about which biological approach is more reliable for creating non-union model. We investigated how to create a reproducible atrophic non-union model in a rat femur. We compared three groups: simple osteotomy (group A), partial periosteum cauterization (group B), and extensive periosteum and bone marrow resection (group C). All samples in group C demonstrated atrophic non-union in radiological, histological, and biomechanical analyses, however half of the samples in group B showed fracture healing at week 16. Extensive resection of periosteum and bone marrow is important for a reproducible atrophic non-union model in a rat femur. [ABSTRACT FROM AUTHOR]

Common traumas to the skeletal system are bone fractures and injury-related articular cartilage damage. The healing process can be impaired resulting in non-unions in 5–10% of the bone fractures and in post-traumatic osteoarthritis (PTOA) in up to 75% of the cases of cartilage damage. Despite the amount of research performed in the areas of fracture healing and cartilage repair as well as non-unions and PTOA, still, the outcome of a bone fracture or articular cartilage damage cannot be predicted. Here, we discuss known risk factors and key molecules involved in the repair process, together with the main challenges associated with the prediction of outcome of these injuries. Furthermore, we review and discuss the opportunities for mass spectrometry (MS) – an analytical tool capable of detecting a wide variety of molecules in tissues – to contribute to extending molecular understanding of impaired healing and the discovery of predictive biomarkers. Therefore, the current knowledge and challenges concerning MS imaging of bone and cartilage tissue as well as in vivo MS are discussed. Finally, we explore the possibilities of in situ, real-time MS for the prediction of outcome during surgery of bone fractures and injury-related articular cartilage damage. [ABSTRACT FROM AUTHOR]

Purpose: There is vast literature supporting valgus osteotomy in fracture neck of femur. However, little or no distinction has ever been made to evaluate the success of the procedure in these two different scenarios-non-unions due to failed osteosynthesis and neglected fractures neck of femur. The aim of our study was to compare the results of valgus osteotomy in neglected neck femur fractures and non-union fractures of neck of femur.Methods: This is a single tertiary centre-based retrospective study. The records of all patients aged less than 45 years who underwent valgus osteotomy for neck of femur fractures from 2012 to 2017 were evaluated. Patients with fracture neck of femur of over one month's duration, where no previous surgical intervention was undertaken were placed in neglected fracture group. Patients with failed primary osteosynthesis surgery, either cannulated cancellous screw or dynamic hip screw, were placed in fixation failure group. There were 23 patients in neglected group and 17 patients in fixation failure group. Demographical details, fracture patterns, and preoperative radiograph, surgery time, blood loss, post-operative complications, union time, and non-unions were studied in both groups.Results: Osteotomy site united in mean time of 11 weeks in fixation failure group and 11.3 weeks in neglected group (p = .434). Time to radiological union of fracture was 16 weeks (12-23 weeks) for neglected fracture group compared to 25 weeks (20-32 weeks) for fixation failure group which was statistically significant (p = .02). Seven out of 17 fractures did not unite in fixation failure group compared to one non-union out of 23 patients in neglected group. (p = .004) There were two loss of fixation with implant failure in fixation failure group compared to none in neglected group (p = .174). Neither of the groups had any surgical site infection.Conclusion: Valgus osteotomy results in excellent union rates for neglected fractures of neck of femur. However, the union rates of valgus osteotomy are lower in neck femur fractures with failed implants compared to neglected fractures and the procedure should be cautiously used in such circumstances. [ABSTRACT FROM AUTHOR]

The available scores to clinically evaluate fracture consolidation encounter difficulties to interpret progression towards consolidation in long-bone non-union, particularly when incorporating biomaterials in the surgical treatment. The aims of this study were to validate the REBORNE bone healing scale in tibia, humerus and femur non-unions treated by a combination of mesenchymal stromal cells (MSCs) and biomaterials, through the interclass correlation (ICC) among raters, and to define reliability and concordance in anteroposterior and lateral radiographs, compared to computed tomography (CT).Methods: Twenty-six cases from the EudraCT 2011-005441-13 clinical trial underwent bone healing evaluation, if at least 3 out of 4 cortical views clearly identified. Three senior orthopaedic surgeons evaluated radiographs and CTs at 3 and 6 months FU. All cases included preoperative imaging and radiographs at 12 months. The 4-stage scale score was obtained from each cortical view in orthogonal radiographs or CTs. A score of 0.6875 (11/16) was set as a threshold for bone healing. Statistically, ICC evaluated agreement among raters. Cronbach's alpha coefficient tested reliability. Lin's concordance correlation coefficients (CCC) were estimated between mean CT scores and mean radiographic scores. Bland and Altman graphs provided the limits of agreement between both imaging techniques. Sensitivity and specificity were assessed in radiographs (against CT), and the Area Under the Receiver Operating Characteristics (ROC) Curve was estimated. The probability to predict bone consolidation with REBORNE scores obtained from radiographs was modelled.Results: An ICC of 0.88 and 0.91 (CT and radiographs) confirmed agreement in the REBORNE score for non-union bone healing, with an inter-rater reliability of 0.92 and 0.95. Scores through the radiographic evaluation were found equivalent to the CTs at 6 months FU. A CCC of 0.79 was detected against CT. The radiographic scores in the REBORNE bone healing scale correctly classified bone consolidation in 77%, with an accuracy of 83% based on ROC curves.Conclusions: The REBORNE score measured with CT or radiographic images was reliable among raters at a follow-up time above 6 months for long bone non-union fractures. The REBORNE scale measured with radiographs proved valid to assess consolidation against CT measurements. [ABSTRACT FROM AUTHOR]

Purpose: Osteogenesis imperfecta (OI) is characterized by increased bone fragility and susceptibility for fractures. A few studies described and compared treatment modalities for femur fractures in children with OI. However, no cohort studies on adults with OI have been published. This study on adult OI patients aims to give insight into the incidence of femur fractures and non-unions and its best treatment options to avert non-union. Methods: In this retrospective, descriptive study of the OI expert clinic in The Netherlands, all medical charts of patients 16 years or older were analyzed for femur fracture incidence, non-union rate and treatment modality. Results: Of 216 OI patients, 34 patients suffered a femur fracture with 12 patients having more than 1 femur fracture. For all types of femur fractures, the incidence was 651 fractures per 100,000 person-years annually. In 49 total fractures, 10 fractures resulted in a non-union, mostly shaft fractures of type 4 OI patients. Surgically treated shaft fractures had the best outcomes for non-union. Conclusions: OI adults were prone to developing femur fractures and non-unions. Especially type 4 OI adults, with conservatively treated shaft fractures, were at high risk for non-unions. [ABSTRACT FROM AUTHOR]

Aim Of the Study: The aim of this case-control study was to develop a clinical decision rule to support assessment of the risk of long-bone non-union and plan for appropriate early intervention.Methods: Two hundred patients (100 cases and 100 controls) were recruited. Risk factors identified to contribute to the development of non-union were recorded and analysed with a multivariable logistic regression model. Tabulation of the outcome (non-union/union) against each risk factor in turn (univariable analysis) was carried out. Odds ratios and confidence intervals were derived using Wald's method. A receiver-operator curve was calculated and the area under the curve was computed. Having established the eight most important risk factors, a non-union risk index was developed as the count of the risk factors present in each patient.Results: The five risk factors for non-union with greater effect size were post-surgical fracture gap > 4 mm (odds ratio (OR) = 11.97 95% CI (4.27, 33.53)), infection superficial/deep (OR 10.16 (2.44, 42.36)), not optimum mechanical stability (OR 10.06 (3.75, 26.97)), displacement > 75% of shaft width (OR 6.81 (2.21, 20.95)), and site of fracture-tibia (OR 4.33 (1.32, 14.14)). The ROC curve for the non-union index was 0.924, sensitivity 91%, specificity 77%.Conclusions: The non-union index derived from counting risk factors predicts union for 0-4 risk factors and non-union for 5-8 risk factors. It can be readily applied and can guide clinicians about the risk of development of long-bone non-union. It can become a powerful aid for assessing fracture fixation outcome and to support early intervention. [ABSTRACT FROM AUTHOR]

The pre-operative determination of infection plays a decisive role in non-union treatment. This study investigated in a large cohort the diagnostic potential of contrast-enhanced ultrasound (CEUS) as stand-alone method for the differentiation between aseptic and infected non-unions. Of 109 patients with lower extremity non-unions (tibia n = 78, femur n = 31) osseous perfusion with CEUS was prospectively assessed before revision surgery. The perfusion was quantified via time-intensity curves and peak enhancement (PE) (arbitrary unit [au]). Significant perfusion differences between aseptic and infected non-unions were evident (PE, p < 0.001). The sensitivity and specificity for the detection of infected tibial and femoral non-unions could be determined with 85.1% and 88.7% (cutoff PE: 81.2 au). CEUS illustrates tibial and femoral non-union perfusion in real time and discriminates reliably between aseptic and infected non-unions. Consequently, when CEUS is integrated into the diagnostic routine algorithm, non-union revision surgery can be planned more accurately as a single or multistep procedure. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic disparities are an inherent and currently unavoidable aspect of medicine. Knowledge of these disparities is an essential component towards medical decision making, particularly among an increasingly diverse population. While healthcare disparities have been elucidated in a wide variety of orthopaedic conditions and management options, they have not been established among patients who present for treatment of an ununited fracture. The purpose of this study is to answer the following questions: 1) Following surgical management of (fracture) non-unions, are there differences in outcomes between differing ethnic groups? 2) Following surgical management of (fracture) non-unions, are there differences in outcomes between patients with differing education levels? 3) Following surgical management of (fracture) non-unions, are there differences in outcome between patients with differing incomes?Methods: Between September 2004 and December 2017, operatively treated patients who presented with a long bone fracture non-union were prospectively followed. These patients presented with a variety of fracture non-unions that underwent surgical intervention. Sociodemographic factors were recorded at presentation. Long-term outcomes were evaluated using the Short Musculoskeletal Function Assessment (SMFA), pain scores, post-operative complications and physical exam at latest follow up. The SMFA is a 46-item questionnaire, assessing patient functional and emotional response to musculoskeletal ailments.Results: Three-hundred-twenty-nine patients met inclusion criteria. Patients with a lower education had worse long-term functional outcomes (P < 0.001) and increased pain scores (P = 0.002) at latest follow-up. Patients who made less than $50,000 annually had worse long-term functional outcomes (P = 0.002) and reported higher pain scores (P = 0.003) following surgical management of (fracture) non-unions. Multiple linear regression demonstrated education level to be an independent predictor of long-term functional outcomes following surgical management of (fracture) non-unions (B= -0.154, 95% Confidence Interval [CI]=-10.96 to -1.26, P = 0.014). No differences existed in outcomes or pain scores between those of different ethnic groups. No differences existed regarding post-operative complications and time to union between patients of different ethnic groups, educational levels and income status.Conclusion: Patients with lower education levels and individuals who make less than $50,000 annually have worse functional outcomes following surgical management of (fracture) non-unions. Orthopaedic trauma surgeons should therefore be aware of these disparities, and consider early interventions aimed at optimizing patient recovery in these subsets. [ABSTRACT FROM AUTHOR]

The large bone defect treatment is a challenge issue in modern orthopaedic trauma surgery. One of the most used technique is the Masquelet's technique. In this case report we used a modified Masquelet technique to fill a six centimeters bone gap in the proximal femur. A 18-year-old boy with a septic pseudoarthrosis was treated with a two stages procedure: in the first step we used a hollow antibiotic spacer and an intramedullary nail. In the second step, we used both omologous (6 cm of bone allograft) and autologous bone graft with a new intramedullary nail. Immediate partial weight bearing was allowed and after 3 months the patient started walking with complete weight bearing. A year later the fracture had healed uneventfully. The modification of the Masquelet Technique that we have made allows the patient to immediately weight bearing safely, speeding up the functional recovery. Further studies are needed to standardize this type of combined technique. [ABSTRACT FROM AUTHOR]

Nonunion of the humeral shaft occurs in 2%-10% of nonsurgically treated fractures and in up to 15% of fractures treated by primary open reduction and internal fixation. Gunshot humerus shaft fractures are a frequent type of injury; the degree of comminution and bone loss, as well as soft tissue disruption may influence the healing process, causing major sequelae with loss of function. Here we describe a 30 years old midshaft nonunion of the humerus, that occurred in a young woman after a gunshot. She was initially treated with hanging cast with definitive nonunion and secondary loss of limb function. After 30 years, careful management of the non union fracture ends, locked intramedullary nailing and bone grafting harvested from the femoral canal using the Reamer Irrigator Aspirator (RIA) system led to union with recovery of limb function. [ABSTRACT FROM AUTHOR]

Bone fractures create five problems that must be resolved: bleeding, risk of infection, hypoxia, disproportionate strain, and inability to bear weight. There have been enormous advancements in our understanding of the molecular mechanisms that resolve these problems after fractures, and in best clinical practices of repairing fractures. We put forth a modern, comprehensive model of fracture repair that synthesizes the literature on the biology and biomechanics of fracture repair to address the primary problems of fractures. This updated model is a framework for both fracture management and future studies aimed at understanding and treating this complex process. This model is based upon the fracture acute phase response (APR), which encompasses the molecular mechanisms that respond to injury. The APR is divided into sequential stages of "survival" and "repair." Early in convalescence, during "survival," bleeding and infection are resolved by collaborative efforts of the hemostatic and inflammatory pathways. Later, in "repair," avascular and biomechanically insufficient bone is replaced by a variable combination of intramembranous and endochondral ossification. Progression to repair cannot occur until survival has been ensured. A disproportionate APR—either insufficient or exuberant—leads to complications of survival (hemorrhage, thrombosis, systemic inflammatory response syndrome, infection, death) and/or repair (delayed- or non-union). The type of ossification utilized for fracture repair is dependent on the relative amounts of strain and vascularity in the fracture microenvironment, but any failure along this process can disrupt or delay fracture healing and result in a similar non-union. Therefore, incomplete understanding of the principles herein can result in mismanagement of fracture care or application of hardware that interferes with fracture repair. This unifying model of fracture repair not only informs clinicians how their interventions fit within the framework of normal biological healing but also instructs investigators about the critical variables and outputs to assess during a study of fracture repair. [ABSTRACT FROM AUTHOR]

Diaphyseal fractures of the femur and tibia are a frequent consequence of trauma and are most often managed with intramedullary nailing. Although outcomes from these fractures are generally perceived as good, it is estimated that 7 to 14% of people with tibial and femoral shaft fractures progress to non-union and an even greater proportion suffer delayed union, which causes substantial health and economic burdens both for patients and health services. Compared to those whose fractures unite within the normal timeframe, patients suffering delayed union or non-union suffer more pain, worse functional outcomes, greater psychological disability and longer amounts of time off work. In response to non-union, invasive and costly secondary procedures such as exchange nailing, supplementary fixation and/or bone grafting are commonly required. We hypothesise that performing acute autologous bone grafting at the time of the primary intramedullary nailing procedure would reduce the incidence of fracture delayed union and non-union for tibial and femoral shaft fractures. The autologous cancellous bone retrieved during reaming with intramedullary nailing is usually discarded. We propose a minimally invasive surgical technique to transplant the retrieved intramedullary reamings to the fracture site during the primary fracture fixation. Autologous cancellous bone grafting is the gold standard for management of fracture non-union, and works by providing osteoprogenitor cells, an osteoconductive scaffold, and growth factors to the fracture site, where they are crucial for fracture healing. Proprietary biological products have also been developed that aim to replicate the results from bone grafting. Although autologous cancellous bone grafting is a proven and robust technique for the treatment of atrophic fracture non-union, it has not been widely studied in the acute management of femoral and tibial shaft fractures. The proposed hypothesis is amenable to testing in randomized clinical trials. If found to be effective in reducing rates of delayed union and non-union with minimal adverse events, this method could be adopted on a large scale, potentially transforming acute management of long bone fractures, and improving patient outcomes from these injuries. [ABSTRACT FROM AUTHOR]

Objective: The objective was to determine if there is a significant difference between rates of non-union of type II and III odontoid fractures in patients with calcium pyrophosphate dihydrate deposition (CPPD) compared with a control population.Materials and Methods: A 10-year retrospective picture archive and communications system review was performed of 31 CPPD patients and 31 control patients. Imaging studies were reviewed for radiographic or CT evidence of osseous union and complications.Results: There was a significant difference in the rates of non-union between the two groups, with the non-union rate reaching 90.3% in the CPPD group and 32% in the control group. Comparing the degree of displacement and angulation of the two groups did not show a significant difference.Conclusion: The results indicate that odontoid fracture non-union rates are significantly higher in CPPD patients and should be taken into consideration when diagnosing odontoid fractures and deciding on appropriate treatment. [ABSTRACT FROM AUTHOR]

Introduction: In the current study, we sought to determine if serum concentrations of MMPs correlate with bone regeneration occurring during the course of the Masquelet-therapy and to identify if MMPs may serve as early biomarkers reflecting successful bone regeneration and tissue remodeling.Material and Methods: This study was designed as a prospective clinical observer study. We compared serum samples over the time of treatment, as a matched-pair analysis, from 10 patients who were treated successfully with the Masquelet-therapy (Responder) with 10 patients who did not respond to the Masquelet-therapy (Non-Responder). The quantitative measurement was performed with Luminex Performance Human High Sensitivity Assays according to manufacturer's instructions. The lab technician performing the Luminex assays was blinded to both patient data and clinical outcome.Results: Analysis of the expression pattern of MMP-2, -8 and -9 showed significant differences between groups. Two days after the first step of the Masquelet therapy Responder showed peak values of MMP-8 and MMP-9 that where significantly higher (p = 0.003 and p = 0.042, respectively) than in Non-Responder. In contrast serum levels of MMP-2 were lower after the first step of the Masquelet therapy in the Non-Responder group. The ratio of MMP-9 and MMP-2 was significantly higher in the Responder group two days after step I (p = 0.031) as well as 4 weeks after step II (p = 0.030).Conclusion: The findings of the current study emphasize the potential role of MMPs as biomarkers in bone remodeling. In particular, a distinct expression of MMP-2 correlates with successful bone regeneration, whereas initial overexpression of MMP-2 serum levels might identify patients that have a higher risk for a poor outcome of the Masquelet-therapy. Furthermore, we were able to introduce the serum analysis of the ratio of MMP-9 and MMP-2 as promising novel modality for early prediction of the outcome of the Masquelet therapy. Further analysis of this ratio over time subsequent to the second step might serve as an early indicator of a favorable response to the induced membrane technique. [ABSTRACT FROM AUTHOR]

Head preservation of an infected neck of femur fracture appears to be extremely rare with no described cases in literature till date. We present the outcome of head salvage in a young adult with an infected neck of femur nonunion who in addition had chronic osteomyelitic sequelae of his entire femur with reactivation of latent infection in the distal femoral diaphysis. Osteosynthesis was performed by means of cancellous screw fixation augmented with bone substitute following a failed attempt at salvage with a valgus intertrochanteric osteotomy. The patient had an excellent functional outcome with near normal hip range of movements at a follow-up of 5 years after union. [ABSTRACT FROM AUTHOR]

An important consideration when counselling patients with midshaft clavicle fractures is whether operative treatment of non-union, if it develops after non-operative treatment, is associated with higher complication rate than acute fracture fixation. The aim of this study is to compare complications and re-operations after open reduction and plate fixation for acute midshaft clavicle fractures versus non-unions. The study was retrospective. There were 90 patients in the acute fixation group and 20 patients in the non-union group. The mean follow-up was 8 and 15 months, respectively, Logistic regression analysis was used to assess whether ‘non-union surgery’ was a predictor of complications and re-operations. Of 90 patients, 23 had complications in acute fixation group. Of 20, 7 developed 8 complications in the non-union group (p = 0.4). Of 90, 12 required re-operations in the acute fixation group compared to 5/20 requiring 7 re-operations in the non-union group (p = 0.19). When any complication or re-operation was considered, ‘non-union surgery’ was not significant predictor for complications (p = 0.78) or re-operations (p = 0.99). The complication and re-operation rates were not higher after non-union surgery compared to acute fracture fixation and were mostly related to persistent delayed or non-union, rather than operative complications. When counselling patients about treatment of midshaft clavicle fractures, a ‘higher complication rate after surgery for non-union, should it happen’ should not be an argument against non-operative treatment. [ABSTRACT FROM AUTHOR]

Background: Fractures of the distal phalanx can result in bony non-union, resulting in acro-osteolysis and subsequent fingertip instability due to soft tissue dissociation from bone. Conventional methods of treating this involve osseous fixation, but do not address the laxity and lack of soft tissue stability with bone. Current techniques also do not address the management of such conditions if bony fragments are too small to reduce. We present a novel method that addresses both soft tissue and bony deformity in this condition. Methods: A review of current techniques in the literature is provided as well as an in depth description of our technique using a representative case. Results: Follow-up results and photographs are presented in this article. Functional assessment is also provided in the article as part of the follow-up. Conclusions: This technique is applicable for cases where severe resorption of distal phalanx has occurred, leaving little or no purchase for bony fixation. Hence, the technique can not only be applied post traumatic acro-osteolysis, but also other conditions where secondary soft tissue lengthening occurs and fingertip instability is formed as a result. [ABSTRACT FROM AUTHOR]

• Cells derived from trabecular bone (HB), healing fracture callus (CA) or fracture nonunion (NU) show homogeneous surface markers expression, but different molecular profiles. • In vitro osteogenic differentiation of cells from NU samples resulted in the highest mineralization compared to those from HB or CA. • Cells from NU samples showed an overactivation of FOS, STAT1, STAT3, JUN and MITF compared to cells from CA. • Increased FOS activity in fracture tissues is associated with the molecular profile of nonunion. Despite the advances in bone fracture treatment, a significant fraction of fracture patients will develop non-union. Most non-unions are treated with surgery since identifying the molecular causes of these defects is exceptionally challenging. In this study, compared with marrow bone, we generated a transcriptional atlas of human osteoprogenitor cells derived from healing callus and non-union fractures. Detailed comparison among the three conditions revealed a substantial similarity of callus and nonunion at the gene expression level. Nevertheless, when assayed functionally, they showed different osteogenic potential. Utilizing longitudinal transcriptional profiling of the osteoprogenitor cells, we identified FOS as a putative master regulator of non-union fractures. We validated FOS activity by profiling a validation cohort of 31 tissue samples. Our work identified new molecular targets for non-union classification and treatment while providing a valuable resource to better understand human bone healing biology. [ABSTRACT FROM AUTHOR]

Purpose: This paper documents the existing evidence on bone morphogenetic proteins (BMPs) use for the treatment of bone fractures, non-union, and osteonecrosis, through a review of the clinical literature, underlying potential and limitations in terms of cost effectiveness and risk of complications.Methods: A systematic review was performed on the PubMed database using the following string: (bone morphogenetic proteins OR BMPs) and (bone repair OR bone regeneration) including papers from 2000 to 2016. The search focused on clinical trials dealing with BMPs application to favor bone regeneration in bone fractures, non-union, and osteonecrosis, in English language, with level of evidence I, II, III, and IV. Relevant data (type of study, number of patients, BMPs delivery material, dose, site, follow-up, outcome, and adverse events) were extracted and analyzed.Results: Forty-four articles met the inclusion criteria: 10 randomized controlled trials (RCTs), 7 comparative studies, 18 case series, and 9 case reports. rhBMP-2 was documented mainly for the treatment of fractures, and rhBMP-7 mainly for non-unions and osteonecrosis. Mixed results were found among RCTs and comparative papers: 11 reported positive results for BMPs augmentation, 3 obtained no significant effects, and 2 showed negative results. The only study comparing the two BMPs showed a better outcome with rhBMP-2 for non-union treatment.Conclusion: Clinical evidence on BMPs use for the treatment of fractures, non-union, and osteonecrosis is still controversial, with the few available reports being mainly of low quality. While positive findings have been described in many studies, mixed results are still present in the literature in terms of efficacy and adverse events. The difficulties in drawing clear conclusions are also due to the studies heterogeneity, mainly in terms of different BMPs applied, with different concomitant treatments for each bone pathology. Therefore, further research with well-designed studies is needed in order to understand the real potential of this biological approach to favour bone healing. [ABSTRACT FROM AUTHOR]

Introduction: Surgical treatment of persistent non-union of the humeral shaft is a complex situation because of the risk of failure and surgery-related complications. The primary objective of this study was to evaluate clinical and radiological results of a continuous series of persistent non-union treated with plating and bone grafting. The secondary objective was to expose factors contributing to the failure of prior bone union attempts.Material and Methods: Sixteen patients (average age of 52 years) were treated for persistent non-union of the humeral shaft in our department; six of these patients had predisposing comorbidities or addictions. The persistent non-union was treated by plating with autologous bone graft from the iliac crest in a single-stage procedure in 12 cases and a two-stage procedure in three cases; one case was treated with plating and vascularized fibula graft.Results: At a minimum follow-up of 12 months (average 78 months), four (25 %) failed to heal. The 12 other patients had bone union after an average of eight months. The average QuickDASH score was 48 points (18-72). A retrospective analysis of the prior attempts to treat the non-union revealed three cases of unstable fixation, four cases with no osteogenic supply and seven cases of positive microbiological cultures at the non-union site.Conclusion: Plating and autologous bone grafting resulted in union in only 75 % of persistent non-union of the humeral shaft. The persistent nature of the humeral shaft non-union could be attributed to deviating from validated rules for surgical treatment and/or the presence of a surgical site infection. [ABSTRACT FROM AUTHOR]

Purpose: The treatment of large bone defects represents a significant challenge for orthopaedic surgeons. In recent years, biologic agents have also been used to further improve bone healing. Among these, platelet-rich plasma (PRP) is the most exploited strategy. The aim of the present study was to systematically review the available literature to identify: 1) preclinical in-vivo results supporting the rational of PRP use for bone healing; 2) evidence from the clinical practice on the actual clinical benefit of PRP for the treatment of fractures and complications such as delayed unions and non-unions.Methods: A systematic review of the literature was performed on the application of PRP in bone healing, using the following inclusion criteria: pre-clinical and clinical reports of any level of evidence, written in English language, published in the last 20 years (1996-2016), on the use of PRP to stimulate long-bone defect treatment, with focus on fracture and delayed/non-unions healing.Results: The search in the Pubmed database identified 64 articles eligible for inclusion: 45 were preclinical in-vivo studies and 19 were clinical studies. Despite the fact that the overall pre-clinical results seem to support the benefit of PRP in 91.1 % of the studies, a more in depth analysis underlined a lower success rate, with a positive outcome of 84.4 % in terms of histological analysis, and even lower values considering radiological and biomechanical results (75.0 % and 72.7 % positive outcome respectively). This was also mirrored in the clinical literature, where the real benefit of PRP use to treat fractures and non-unions is still under debate.Conclusion: Overall, the available literature presents major limitations in terms of low quality and extreme heterogeneity, which hamper the possibility to optimize PRP treatment and translate it into a real clinical benefit despite positive preclinical findings on its biological potential to favour bone healing. [ABSTRACT FROM AUTHOR]

Introduction: Non-union perfusion can be visualized with dynamic contrast-enhanced (DCE) MRI. This study evaluated DCE-MRI to predict non-union consolidation after surgery and detect factors that affect bone healing.Materials and Methods: Between 2010 and 2015 non-union perfusion was prospectively quantified in 205 patients (mean age, 51.5 years, 129 men, 76 women) before intervention and at 6, 12, 26, 52 and more weeks follow-up. DCE-MRI results were related to the osseous consolidation, the ability to predict successful outcome was estimated by ROC analysis. The relevance of the body mass index (BMI) and the non-union severity score (NUSS) to the healing process was assessed.Results: Tibial (n=99) and femoral (n=76) non-unions were most common. Consolidation could be assessed in 169 patients, of these 103 (61%) showed eventual healing and demonstrated higher perfusion than in failed consolidation at 6 (p=0.0226), 12 (p=0.0252) and 26 (p=0.0088) weeks follow-up. DCE-MRI at 26 weeks follow-up predicted non-union consolidation with a sensitivity of 75% and a specificity of 87% (false classification rate 19%). Higher BMI (p=0.041) and NUSS (p<0.0001) were associated with treatment failure.Conclusions: DCE-MRI perfusion analysis after non-union surgery predicts successful outcome and could facilitate the decision of early intervention. NUSS and BMI are important prognostic factors concerning consolidation. [ABSTRACT FROM AUTHOR]

Background: The number of patients with total hip replacement (THR) is likely to grow. Periprosthetic femoral fractures occur in 0.1-4.5 % of patients with THR. Treatment of periprosthetic fractures in the vicinity of well-fixed implants has focused on lateral plating. The purpose of this study was to evaluate polyaxial locking plate treatment of periprosthetic fractures with THR in regard to fracture type, surgical procedure, complications, and outcome. Methods: Between 2007 and 2013, 109 patients underwent surgical treatment for periprosthetic femur fractures with 66 fractures in the vicinity to a THR. Fifteen patients were excluded. Therefore, 51 patients with a mean age of 78.7 years were identified. There were 76.5 % females. Average BMI was 27.1 kg/m. Follow-up averaged 25 months. Total hip stems were uncemented in 63 %. Low-energy mechanism predominated. Fractures were classified according to AO/OTA and Vancouver classifications with the majority (70.6 %) classified as AO/OTA type A fractures. Surgeries were performed utilizing a polyaxial locking plate. Complications were recorded concerning infection, union, fixation failure, and revision surgery. Results: After the index procedure, 90.2 % healed. Non-union formation was diagnosed in 5.9 % with 2.0 % leading to hardware failure. All patients with non-union formation had interprosthetic fractures ( χ = 0.016). Additionally, these fractures were classified as AO/OTA type B fractures ( χ = 0.003). Conclusions: Surgical management despite polyaxial locked plate fixation continues to be challenging and may still result in non-union formation. Non-union formation is increased in AO/OTA type B fractures and related to interprosthetic fractures. Level of evidence: Level IV. [ABSTRACT FROM AUTHOR]

Bone defects remain a challenge for patients and orthopaedic surgeons. Autologous transfer of cancellous bone grafts remains the standard of care. However, in recent years various osteoinductive substitute materials, such as platelet rich plasma (PRP) and hyperbaric oxygen therapy (HBO) have been shown to improve bone healing. This study evaluates the effects of a combined application of PRP and HBO with autologous bone grafting in an animal model. In 48 New Zealand White rabbits bone defects at the radius were filled with autologous bone harvested at the iliac crest. This was combined with application of autologous PRP and/or HBO treatment for the duration of this study. After 3 and 6 weeks histomorphometric, immunohistochemical and radiologic evaluations were performed. All animals tolerated the treatment well. Improved bone regeneration was shown in all groups at 6 weeks compared to 3 weeks. Additional application of PRP and HBO resulted in an increase in new bone formation and increased neovascularization at 3 and 6 weeks. There was no statistical significant difference between PRP and HBO application in these regards. A combinatory use of PRP and HBO resulted in an increased bone regeneration and neovascularization compared to all other groups. This study provides evidence for an improvement of bone regeneration with the combinatory application of PRP and HBO to autologous cancellous bone grafts in a model of weight bearing bone defects in rabbits. Also synergistic effects of these two measures on angiogenesis were evident. [ABSTRACT FROM AUTHOR]

Objective: Non-union after intramedullary nail fixation of femur shaft fractures is although infrequent but a challenging condition to treat. The treatment options available to deal with such a situation include exchange nailing, removal of nail and re-osteosynthesis with plating, or Ilizarov fixation. We believe that rotational instability, in the presence of a nail, is one of the main reasons for most of the non-union. We present our experience of plate augmentation leaving the nail in situ for non-union of femoral shaft fracture. Methods: In this retrospective study, we had operated 16 cases of the femoral shaft non-union, which were treated by plate augmentation and bone grafting (if needed) with retention of the intramedullary interlocking nail in situ. The cases of infected non-union and any fracture less than one-year duration were excluded from the study. Results: Bone grafting was done only in 4 cases with atrophic non-union. We could achieve union in all the cases at an average time of 6.25 months. The average time of surgery between the primary surgery of interlocking nail fixation and the plate augmentation was 13 months. Mean surgical time for plate augmentation and bone grafting was 71 min. No major complication or implant failure was encountered. An average residual shortening of the limb was 0.9 cm and average range of motion of the knee was 115°. Conclusion: Plate augmentation seems an effective, reliable, safe and an easy procedure for the treatment of femoral shaft non-union after an intramedullary nailing. [ABSTRACT FROM AUTHOR]

Non-union fractures have considerable clinical and economic burdens and yet the underlying pathogenesis remains largely undetermined. The fracture healing process involves cellular differentiation, callus formation and remodeling, and implies the recruitment and differentiation of mesenchymal stem cells that are not fully characterized. C-X-C chemokine receptor 4 (CXCR4) and Insulin-like growth factor 1 receptor (IGF-1R) are expressed in the fracture callus, but their interactions still remain elusive. We hypothesized that the regulation of CXCR4 by IGF-1R signaling is essential to maintain the bone homeostasis and to promote fracture repair. By using a combination of in vivo and in vitro approaches, we found that conditional ablation of IGF-1R in osteochondroprogenitors led to defects in bone formation and mineralization that associated with altered expression of CXCR4 by a discrete population of endosteal cells. These defects were corrected by AMD3100 (a CXCR4 antagonist). Furthermore, we found that the inducible ablation of IGF-1R in osteochondroprogenitors led to fracture healing failure, that associated with an altered expression of CXCR4. In vivo AMD3100 treatment improved fracture healing and normalized CXCR4 expression. Moreover, we determined that these effects were mediated through the IGF-1R/Insulin receptor substrate 1 (IRS-1) signaling pathway. Taken together, our studies identified a novel population of endosteal cells that is functionally regulated through the modulation of CXCR4 by IGF-1R signaling, and such control is essential in bone homeostasis and fracture healing. Knowledge gained from these studies has the potential to accelerate the development of novel therapeutic interventions by targeting CXCR4 signaling to treat non-unions. • Non-union fracture is a debilitating condition in which bone fails to heal. • IGF-1 has been shown to promote fracture healing, and IGF-1 levels correlate with outcomes of non-union treatments. • Tight regulation by the IGF-1R-IRS1 pathway of CXCR4 expression plays a key role in bone homeostasis and fracture healing. • Treatment with AMD3100 (a CXCR4 antagonist) can improve healing in the non-union caused by IGF-1R deficiency. [ABSTRACT FROM AUTHOR]